WO2017168454A2 - Nouveaux composés utilisés comme inhibiteurs de btk - Google Patents

Nouveaux composés utilisés comme inhibiteurs de btk Download PDF

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Publication number
WO2017168454A2
WO2017168454A2 PCT/IN2017/050127 IN2017050127W WO2017168454A2 WO 2017168454 A2 WO2017168454 A2 WO 2017168454A2 IN 2017050127 W IN2017050127 W IN 2017050127W WO 2017168454 A2 WO2017168454 A2 WO 2017168454A2
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WO
WIPO (PCT)
Prior art keywords
alkyl
hydrogen
group
cycloalkyl
nitrogen
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/IN2017/050127
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English (en)
Other versions
WO2017168454A3 (fr
Inventor
Prabal Sengupta
V.S.N. Murty KADIYALA
Dipali Manubhai DESAI
Sabbirhusen Yusufbhai CHIMANWALA
Tushar Mukund JARAG
Gaurav Sanjivkumar Sheth
Trinadha Rao Chitturi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Sun Pharma Advanced Research Co Ltd
Original Assignee
Sun Pharma Advanced Research Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Sun Pharma Advanced Research Co Ltd filed Critical Sun Pharma Advanced Research Co Ltd
Publication of WO2017168454A2 publication Critical patent/WO2017168454A2/fr
Anticipated expiration legal-status Critical
Publication of WO2017168454A3 publication Critical patent/WO2017168454A3/fr
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings

Definitions

  • Rg, R9, Rjo are independently selected from a group consisting of hydrogen, d-6 alkyl, d-6 cycloalkyl, d-6 haloalkyl, d-6 halocycloalkyl, d-6 hydroxylalkyl, C 3 _6 hydroxycycloalkyl, d-6 alkyl-0-C 3 _ 6 cycloalkyl, CN, C(0)NR 12 Ri 3 , (CH 2 ) n C(0)NR 12 Ri , d-6 cyanoalkyl, C(0)OH, C(0)Od_ 6 alkyl, (CH 2 ) n C(0)OH, (CH 2 ) n dO)Od-6 alkyl, (CH 2 ) n NR 12 R 13 , C 4 _7 heterocycloalkyl wherein the heteroatom is selected from oxygen, sulfur or N(R 14 );
  • R 12 and R 13 together with the nitrogen atom to which they are attached forms a 4 to 7 membered heterocyclic ring optionally containing 1 or 2 additional heteroatoms selected from oxygen and nitrogen; wherein the heterocyclic ring is unsubstituted or substituted with Ci-3 alkyl;
  • R 14 is selected from hydrogen, d-6 alkyl, C 3 _6 cycloalkyl, Ci_6 haloalkyl, Ci_6 hydroxyalkyl, Ci_6 alkyl-0-Ci_6 alkyl, Ci_6 aminoalkyl and C 3 _6 cycloalkyl-0-Ci_6 alkyl; wherein the alkyl and the cycloalkyl groups are optionally substituted with 5 or 6 membered heterocycloalkyl containing 1 or 2 heteroatoms selected from oxygen, sulfur and nitrogen;
  • R 2 is a group selected from
  • R 38 is selected from hydrogen, -Cj_6 alkyl, -C 2 _6 alkenyl, -C 3 _ 7 cycloalkyl;
  • J is absent or -C(O)-
  • G is an electron withdrawing group selected from -C(0)OR 4 o, -C(0)N(R 4 o)2, -CN, -NO 2 , - SO3H, -S02N(R 4 o)2, -SO2R40 wherein R 4 o at each occurrence is independently selected from hydrogen, -Ci -3 alkyl and -C 4 _6 cycloalkyl;
  • W is CH and group A is substituted on W.
  • D is phenyl unsubstituted or substituted with one or more groups selected from halogen or d- 6 alkyl;
  • the present invention provides a compound of Formula I, wherein L is nitrogen and R 3 and R4 taken together with the nitrogen and L to which they are attached respectively, forms a 5 or 6 membered heterocyclic ring.
  • the heterocyclic ring is selected from piperazinyl, imidazolidinyl or hexahydropyrimidinyl.
  • the heterocyclic ring is piperazinyl.
  • n is 1 and R 1 2 and R13 together with the nitrogen atom to which they are attached forms a 6 membered heterocyclic ring containing 1 additional nitrogen atom substituted with methyl; preferably the heterocyclic ring is piperazinyl;
  • Rj and R 2 together with the nitrogen atom to which they are attached forms 6 membered heterocycloalkyl containing 1 additional nitrogen atom which is substituted with methyl.
  • the hydrazines prepared as per the process provided in Schemes 1 to 4 were treated with aromatic electrophiles to obtain N-aryl/ heteroarylhydrazines belonging to Formula I.
  • Some of the representative aromatic electrophilic compounds are provided in Figure-6.
  • the aromatic electrophilic compound may also require some functional modifications depending upon the type of the substitution on them and such modifications are under the purview of a person skilled in the art.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne de nouveaux composés de Formule (I) utilisés comme inhibiteurs de tyrosine kinase de Bruton, leur procédé de préparation, et l'utilisation des composés dans la préparation de compositions pharmaceutiques pour le traitement thérapeutique de troubles impliquant une médiation de la tyrosine kinase de Bruton chez l'homme.
PCT/IN2017/050127 2016-04-02 2017-04-03 Nouveaux composés utilisés comme inhibiteurs de btk Ceased WO2017168454A2 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
IN201621011745 2016-04-02
IN201621011745 2016-04-02
IN201621023892 2016-07-12
IN201621023892 2016-07-12

Publications (2)

Publication Number Publication Date
WO2017168454A2 true WO2017168454A2 (fr) 2017-10-05
WO2017168454A3 WO2017168454A3 (fr) 2018-10-11

Family

ID=59962693

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IN2017/050127 Ceased WO2017168454A2 (fr) 2016-04-02 2017-04-03 Nouveaux composés utilisés comme inhibiteurs de btk

Country Status (1)

Country Link
WO (1) WO2017168454A2 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180099959A1 (en) * 2016-12-13 2018-04-12 Princeton Drug Discovery Inc Protein kinase inhibitors
WO2022086284A1 (fr) * 2020-10-23 2022-04-28 (주)메디톡스 Inhibiteur de protéine kinase et son utilisation
US12441707B2 (en) 2019-12-30 2025-10-14 Tyra Biosciences, Inc. Indazole compounds

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
PL215901B1 (pl) * 1999-04-15 2014-02-28 Bristol Myers Squibb Co Cykliczny inhibitor bialkowych kinaz tyrozynowych, jego zastosowanie oraz kompozycja farmaceutyczna zawierajaca taki zwiazek
WO2011009226A1 (fr) * 2009-07-22 2011-01-27 北京莱博赛路森药物科技有限公司 Procédé de préparation de dérivés de dasatinib utiles en tant qu’agents antitumoraux et leurs intermédiaires

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20180099959A1 (en) * 2016-12-13 2018-04-12 Princeton Drug Discovery Inc Protein kinase inhibitors
US10479786B2 (en) * 2016-12-13 2019-11-19 Princeton Drug Discovery, Inc Protein kinase inhibitors
US10556897B2 (en) 2016-12-13 2020-02-11 Princeton Drug Discovery, Inc Protein kinase inhibitors
US11236080B2 (en) 2016-12-13 2022-02-01 Princeton Drug Discovery, Inc Protein kinase inhibitors
US12441707B2 (en) 2019-12-30 2025-10-14 Tyra Biosciences, Inc. Indazole compounds
WO2022086284A1 (fr) * 2020-10-23 2022-04-28 (주)메디톡스 Inhibiteur de protéine kinase et son utilisation

Also Published As

Publication number Publication date
WO2017168454A3 (fr) 2018-10-11

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